Mesothelioma Research in Australia Focuses on Blocking Protein Growth

Sonja Klebe, an associate professor in the Anatomical Pathology Department at Flinders University in Australia, has no illusions about her latest mesothelioma research.

She isn’t expecting to find a cure. She is expecting to uncover a better way to treat patients.

“There is a real need to offer more, and newer therapies,” Klebe told Asbestos.com. “I really do think we need new strategies, and fast. I think what we are doing (in our research) has the potential to slow the progression (of mesothelioma) and alleviate symptoms a lot.”

Klebe is leading a first-of-its-kind research project that uses both drugs and gene therapy to block two different proteins simultaneously that often stimulate the growth of mesothelioma tumors.

“We know that blocking growth factors alone can delay the progression of cancer growth, and so does blocking membrane proteins alone,” she said. “But no one knows what happens when you block them together. We are the first to use the pharmacological blocker, and the first to try a combination therapy.”

Blocking Tumor Growth

Mesothelioma is the rare but aggressive cancer that is caused by repeated exposure to microscopicasbestos fibers, which can be accidentally inhaled and become lodged in the thin lining around the lungs.

For a tumor to grow, it must secrete proteins that signal the blood vessels to send nutrients. Blocking the proteins has been a focus of considerable research in the past, yet the current therapies have not reflected much progress.

“The survival for patients with mesothelioma has not significantly changed in the last 15 years,” Klebe said. “And only very limited, new therapies have been tested.”

Australia’s High Rate of Mesothelioma

Australia has one of the highest per-capita rates of mesothelioma in the world, estimated at 700 new cases annually. Klebe expects mesothelioma to peak in 2020 at 900 new cases. Although Australia is one of more than 50 counties that have banned the use of asbestos in manufacturing, the lengthy latency period (10 to 50 years) of the disease, and the continued exposure to aging asbestos fibers will keep the rate high.

Klebe said her combination therapy will be tested on its ability to stop metastases of mesothelioma, and also to make sure it does not damage healthy cells. The research will use human cells collected from the pleural effusion fluid that was extracted from patients.

“We are looking at two different molecules,” she said. “They both help the mesothelioma to grow, but the pathways they do it with are different. By using two molecules that are important simultaneously, we hope to hit the tumor cells more effectively.”

She also believes the two proteins involved can serve as prognostic markers to better predict individual survival rates.

“We know that if a patient has high levels of the growth factor in their blood, they will die quicker, but we’ve now discovered that increased levels of the membrane protein also are associated with survival,” she said.

The most effective therapy in the past has been an aggressive surgery, removing either the lining surrounding the lung, or both the lining and an entire lung. Surgery, though, is only an option if the mesothelioma has not spread. Less than 25 percent of pleural mesothelioma patients are even candidates for surgery. Many are too old or frail to survive it.

“We are hoping that our proposed therapy would likely be suitable for those patients who cannot undergo those aggressive (surgery) treatments,” Klebe said. “The number (of mesothelioma patients) is still rising. Until you actually go to the clinical trial, you don’t know for sure what will happen.”